Creating a new benzaldehyde lyase for atom-economic synthesis of chiral 1,2,4-butanetriol and 2-aminobutane-1,4-diol from formaldehyde

Summary While formaldehyde is an emerging C1 resource for the synthesis of high value-added chemicals due to its high and versatile reactivity, selective activation and controllable transformation of formaldehyde still remains a great challenge. In particular, coupling of formaldehyde with small aldehydes such as 3-hydroxypropanal offers excellent opportunity for constructing valuable molecules but has not been realized. A benzaldehyde lyase from Herbiconiux sp. SALV-R1 was engineered through directed evolution to achieve the coupling of 3-hydroxypropanal and formaldehyde. A carbonyl reductase and a transaminase were identified to catalyze reduction or transamination of 1,4-dihydroxybutan-2-one, a highly functionalized small ketone. The newly attained enzymatic hydroxymethylation and asymmetric reduction or transamination were then combined with the chemocatalytic hydration of acrolein in a one-pot process to synthesize optically pure 1,2,4-butanetriol and 2-aminobutane-1,4-diol from acrolein and formaldehyde. These results exemplify a new way for sustainable synthesis of high value-added chemicals from C1 molecules and simple starting materials.